From the Peripheral Vascular Surgery Society

Management of in-sent restenosis after carotidartery stenting in high-risk patientsWei Zhou, MD, Peter H. Lin, MD, Ruth L. Bush, MD, Eric K. Peden, MD, Marlon A. Guerrero, MD,Panagiotis Kougias, MD, and Alan B. Lumsden, MD, Houston, Tex

Background: Carotid artery stenting (CAS) has emerged as an acceptable treatment alternative in patients with carotidbifurcation disease. Although early results of CAS have been promising, long-term clinical outcomes remain less certain.We report herein the frequency, management, and clinical outcome of in-stent restenosis (ISR) after CAS at a singleacademic institution.Methods: Clinical records of 208 CAS procedures in 188 patients with carotid stenosis of 80% or greater, including 48(26.5%) asymptomatic patients, during a 42-month period were analyzed. Follow-up serial carotid duplex ultrasoundscans were performed. Selective angiography and repeat intervention were performed when duplex ultrasound scansshowed 80% or greater ISR. Treatment outcomes of ISR interventions were analyzed.Results: Over a median 17-month follow-up, 33 (15.9%) ISRs of 60% or greater were found, according to the Dopplercriteria. Among them, seven patients (3.4%) with a mean age of 68 years (range, 65-87 years) developed high-grade ISR(>80%), and they all underwent further endovascular interventions. Six patients with high-grade ISR were asymptom-atic, whereas one remaining patient presented with a transient ischemic attack. Five of seven ISRs occurred within 12months of CAS, and two occurred at 18 months’ follow-up. Treatment indications for initial CAS in these seven patientsincluded recurrent stenosis after CEA (n � 4), radiation-induced stenosis (n � 1), and high-cardiac-risk criteria (n � 2).Treatment modalities for ISR included balloon angioplasty alone (n � 1), cutting balloon angioplasty alone (n � 4),cutting balloon angioplasty with stent placement (n � 1), and balloon angioplasty with stent placement (n � 1).Technical success was achieved in all patients, and no periprocedural complications occurred. Two patients withpost-CEA restenosis developed restenosis after ISR interventions, both of whom were successfully treated with cuttingballoon angioplasty at 6 and 8 months. The remaining five patients showed an absence of recurrent stenosis or symptomsduring a mean follow-up of 12 months (range, 3-37 months). By using the Kaplan-Meier analysis, the freedom from 80%or greater ISR after CAS procedures at 12, 24, 36, and 42 months was 97%, 97%, 96%, and 94%, respectively.Conclusions: Our study showed that ISR after CAS remains uncommon. Successful treatment of ISR can be achieved byendovascular interventions, which incurred no instance of periprocedural complications in our series. Patients whodeveloped ISR after CEA were likely to develop restenosis after IRS intervention. Diligent ultrasound follow-up scans are

important after CAS, particularly in patients with post-CEA restenosis. ( J Vasc Surg 2006;43:305-12.)

Since balloon angioplasty and stent placement in thecarotid artery was first introduced more than a decade ago,1

this treatment paradigm has become increasingly adaptedin the medical community. Despite an increased volume ofcarotid artery stenting (CAS) being performed worldwide,carotid endarterectomy (CEA) remains the standard treat-ment in patients with carotid occlusive disease. As reportedin a recent consensus statement from the American HeartAssociation, this minimally invasive procedure should beoffered to a limited group of high-risk patients. Thesehigh-risk patients include those with severe cardiopulmo-nary comorbidities, recurrent stenosis after endarterec-tomy, prior neck irradiation, and inaccessible lesions abovethe C2 level.2,3

From the Division of Vascular Surgery & Endovascular Therapy, Michael E.DeBakey Department of Surgery, Baylor College of Medicine, Michael E.DeBakey VA Medical Center.

Competition of interest: none.Presented at the Annual Meeting of the Peripheral Vascular Surgery Society,

Chicago, Ill, Jun 15-18, 2005.Reprint requests: Peter H. Lin, MD, Michael E. DeBakey Department of

Surgery, Baylor College of Medicine, Houston VAMC (112), 2002Holcomb Blvd, Houston, TX 77030 (e-mail: plin@bcm.tmc.edu).

0741-5214/$32.00Copyright © 2006 by The Society for Vascular Surgery.

doi:10.1016/j.jvs.2005.10.040

The short-term efficacy of CAS when compared withCEA has been studied in several large prospective trials.The Carotid and Vertebral Artery Transluminal Angio-plasty Study, which evaluated patients with high-gradecarotid stenosis undergoing either CEA or balloon angio-plasty, showed similar clinical outcomes between the twotreatment modalities during the 3 years of follow-up.4

Additionally, the SAPPHIRE trial confirmed that CAS witha distal protection device performed similarly to the endar-terectomy. Moreover, patients treated with CAS experi-enced a significantly lower rate of perioperative myocardialinfarction in contrast to the CEA group.5,6 A study reportedby our group also revealed that CAS with routine use of acerebral protection device is a feasible and effective treat-ment in high-risk patients with carotid occlusive disease.7

Despite the early promising results of these reports,questions remain regarding the long-term durability of thisendovascular treatment modality.8-11 Reports suggesting alow incidence of CAS-related in-stent restenosis (ISR) werelargely derived from studies with relatively small samplesizes and short follow-up periods.8-13 The purposes of thisstudy were to examine the incidence of CAS-associated ISRin our clinical experiences and to assess the durability of

endovascular intervention in the management of ISR.

305

JOURNAL OF VASCULAR SURGERYFebruary 2006306 Zhou et al

MATERIALS AND METHODS

Hospital charts and clinical records were reviewed for allpatients who underwent CAS over a 42-month period end-ing in May 2005. All CAS procedures were performed byvascular surgeons at Baylor College of Medicine–affiliatedhospitals, including the Michael E. DeBakey VA MedicalCenter and the Methodist Hospital. Carotid duplex scanswere performed before the stenting procedure, and high-grade carotid stenosis was documented in all patients.High-risk patients with symptomatic carotid stenosis 80%or greater and asymptomatic carotid stenosis 80% orgreater were considered for the stenting protocol. Proce-dural indications, techniques, and treatment outcomes wereanalyzed.

Patient selection criteria. Eligibility for high-risk pa-tients undergoing CAS was largely based on criteria estab-lished at a recent consensus conference that included variousanatomic considerations, such as high carotid bifurcation(higher than the C2 level), contralateral carotid occlusion,presence of tracheostomy, history of ipsilateral neck irradi-ation, prior radical neck dissection, or CEA.3 The high-riskcriteria also included patients with one or more medicalcomorbidities, such as those myocardial infarction or strokein the previous 3 months. High-risk pulmonary dysfunc-tion included patients with steroid-dependent chronic ob-structive pulmonary disease or a measured forced expira-tory volume in 1 second less than 30% of predicted or lessthan 1 L/s. Finally, high-risk cardiac dysfunction includedthose with a left ventricular ejection fraction less than 30%and documented heart failure (stage III or IV of the NewYork Heart Association classification).

Stenting technique. The antithrombotic protocol forcarotid stenting has been described previously. The patientwas given clopidogrel (75 mg/d) and aspirin (81 mg/d)beginning 3 days before the intervention. After the stentingprocedure, clopidogrel was continued for 3 months, andaspirin was continued for life. Before June 2002, all patientsundergoing carotid stenting received an intravenous (IV)heparin bolus (100 U/kg) to achieve systemic anticoagu-lation during the carotid intervention. After June 2002, theintraoperative anticoagulation regimen was changed to anIV bivalirudin bolus (0.75 mg/kg) followed by an infusionrate of 2.5 mg · kg�1 · h�1. At the completion of thecarotid stenting, IV bivalirudin was discontinued.

All carotid stenting procedures were performed in theoperating room with routine use of embolization protec-tion devices (EPD). A team consisting of two staff physi-cians performed the carotid stenting procedure by usingeither an endovascular operative suite (Siemens; SiemensMedical Systems Inc, Iselin, NJ) or a mobile fluoroscopicunit (OEC 9800; GE Medical Systems, Fairfield, CT). Ananesthesiologist was present to monitor the blood pressureas recorded by an arterial line. Oximetry and continuouselectrocardiography were similarly monitored. The tech-nique of stenting has been described previously.7 Briefly, a7F, 90-cm carotid guiding sheath (Boston Scientific, Natick,

Mass) was placed in the distal common carotid artery

(CCA) by tracking over the 0.035-inch stiff Glidewire orAmplatz guidewire (Boston Scientific). The stiff wire wasroutinely positioned in the external carotid artery to facili-tate advancement of the guide sheath. The stiff guidewirewas next removed, and selective digital carotid angiogramwas performed via the sideport of the guiding sheath.Biplanar intracranial injections were also performed to doc-ument cerebral vasculature. A 0.018-inch guidewire systemwith the EPD was then manipulated to cross the internalcarotid lesion. After the activation of the EPD, a coaxialangioplasty balloon was used to predilate the carotid lesionif necessary. Next, a self-expanding monorail carotid stent(Wallstent [Boston Scientific] or Acculink [Guidant, SantaClara, Calif]) was deployed across the internal carotid ste-nosis. Poststenting balloon angioplasty was performed witheither a 5- or 6-mm-diameter angioplasty balloon, depend-ing on the appearance of the completion angiogram. Com-pletion angiogram, including biplanar carotid and cerebralviews to document the vascular anatomy and to excludecerebral thromboembolism, was performed before the cap-ture of the EPD. The shuttle sheath was subsequentlyremoved, and the groin puncture site was routinely closedwith a 6F femoral closure device (Perclose; Abbott Labo-ratories, North Chicago, Ill).

Surveillance protocol. Patients were routinely kept inthe hospital overnight and discharged home on the follow-ing day. Follow-up visits with carotid duplex ultrasoundscans were performed at 1, 6, and 12 months after the inter-vention and each year thereafter. Patients who requiredinterventions for clinically significant restenosis after CASwere evaluated with duplex ultrasound scans at 3-monthintervals. All duplex ultrasound scans were performed atapproved vascular laboratories accredited by the Intersoci-ety Commission on Accreditation of Vascular Laboratories.The surveillance studies were performed by seven experi-enced ultrasonographers.

The velocity criteria used to evaluate carotid arterystenosis were modified from the University of Washingtoncriteria and were validated in our laboratories. Briefly, peaksystolic velocity greater than 125 cm/s, end-diastolic ve-locity less than 140 cm/s, and an internal carotid arteryICA/CCA ratio less than 3.2 correlates with 50% to 59%stenosis; ICA/CCA between 3.2 and 4 correlates with 60%to 69% stenosis; ICA/CCA greater than 4 correlates with70% to 79% stenosis; and end-diastolic velocity greater than140 cm/s correlates with greater than 80% stenosis. Addi-tionally, luminal reductions on grayscale images and colorflow disturbances were further evaluated. This is particu-larly important for poststent surveillance. Clinically signifi-cant stenosis was defined as luminal reduction of 80% orhigher. High-grade in-stent stenosis, identified by ultra-sonography, was further verified by biplanar carotid an-giography, and the stenosis was measured geometrically onthe basis of the North American Symptomatic CarotidEndarterectomy Trial criteria. Carotid angioplasty and pos-sible stenting were subsequently performed by following

the standard protocol upon confirmation of the lesions.

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Statistical analysis. Clinical variables that may be as-sociated with restenosis after CAS were analyzed. For thepurposes of this analysis, we compared relevant clinical datain patients with no ISR versus those with a moderate degreeof ISR (�60%). Wilcoxon rank sum tests, �2 analyses, orpaired Student t tests were performed where appropriate.Kaplan-Meier methods were also used to analyze the pa-tency data. The procedural success rates were based on theprimary success of CAS. The test results were consideredsignificant at a P � .05. All statistical analyses were per-formed with the StatView software program (SAS Institute,Cary, NC).

RESULTS

Patient characteristics. A total of 208 CAS procedureswere performed in 188 patients, including 48 (26.5%) asymp-tomatic patients, during the study period. They included163 men and 25 women with a mean age of 69.3 years(range, 55-87 years). Among them, 33 patients (15.9%)developed moderate ISR of 60% or greater on post-CASduplex ultrasonography. Epidemiologic data, preproce-dural risk factors, and presenting symptoms were similarbetween patients without ISR and those with moderate ISR(Table I). When the indications for CAS were comparedbetween these two groups, a significantly higher propor-tion of patients with ISR had post-CEA stenosis (58%)when compared with those who did not have significantISR (11%; P � .03; Table I).

Clinical outcomes. Technical success was achieved in204 (98%) of the 208 CAS procedures. Four procedureswere considered technical failures: three were due to thesevere tortuosity of the aortic arch, which precluded safeadvancement of the guiding catheter, and the fourth wasdue to failure in traversing the carotid stenosis. Among the204 successful CAS cases, the carotid artery stenosis de-creased from 85% � 12% (mean � SD) before the stentplacement to a poststenting mean residual stenosis of10% � 5%. Monorail Wallstents were used in 176 (86%)CAS procedures, and Acculink stents were placed in theremaining 28 (14%) carotid arteries. All stenting proce-dures were performed by using an EPD, including thePercuSurge Guardwire device (Medtronic, Santa Rosa,Calif; n � 22; 11%), the Filterwire system (Boston Scien-tific; n � 154; 75%), or an Accunet EPD (Guidant; n � 28;14%). The overall 30-day stroke and death rate was 2.4%(n � 5). This included one hemispheric stroke due toimmediate carotid stent thrombosis, which was successfullytreated with rheolytic thrombectomy. Three patients diedof myocardial infarction after discharge at 22 days, 6months, and 10 months, and one patient died of respiratoryfailure 5 months later. There was no difference in theoverall complication rate between symptomatic and asymp-tomatic patients (7.3% and 5.9%, respectively). Similarly,no significant differences in overall stroke and death rateswere noted between the symptomatic and asymptomaticgroups (5.9% and 1.8%, respectively). The mean in-hospitallength of stay was 1.7 � 1.4 days. With Kaplan-Meier

analysis, the rates of freedom from 80% or greater ISR after

CAS procedures at 12, 24, 36, and 42 months were 97%,97%, 96%, and 94%, respectively (Fig 1). The rates offreedom from 60% or greater restenosis at 12, 24, 36, and42 months were 97%, 95%, 92%, and 92%, respectively (Fig2). Six patients had groin hematoma, including one patientwho required blood transfusion and one patient who de-veloped a common femoral artery pseudoaneurysm. Nogroin infection was observed in our series.

Follow-up and in-stent stenosis. During a medianfollow-up of 17 months (range, 3-20 months), five patientswere lost to follow-up. Seven patients were found to have80% or greater ISR that was confirmed by angiographyand subsequently treated with endovascular interventions.They were six men and one woman with a mean age of68 years (range, 65-87 years). No differences in ISR werenoted among different carotid stents or EPD devices. Sim-ilarly, no difference in outcome was found when comparingpatients who received poststenting balloon angioplasty

Table I. Comparison of demographic characteristics,clinical symptoms, comorbidities, and CAS indicationsof patients without significant ISR and patients withISR 60% or greater

Variable

Nosignificant

ISR

ModerateISR

(�60%)P

value

Total no. patients 155 33Age, y (mean � SD) 69 � 11 67 � 16 NSMale sex 126 (81%) 27 (82%) NSAsymptomatic carotid lesion 39 (25%) 9 (27%) NSSymptomatic carotid lesion

Stroke 28 (18%) 8 (24%) NSTransient ischemic attack 52 (34%) 11 (33%) NSAmaurosis fugax 36 (23%) 5 (15%) NS

ComorbiditiesCoronary artery disease 115 (74%) 23 (70%) NSCongestive heart failure 33 (21%) 6 (18%) NSHistory of myocardial

infarction 39 (25%) 9 (27%) NSSmoking 113 (73%) 23 (70%) NSHypertension 121 (78%) 26 (79%) NSDiabetes 53 (34%) 10 (30%) NSChronic obstructive

pulmonary disease 37 (24%) 8 (24%) NSHypercholesterolemia 59 (38%) 12 (36%) NSRenal insufficiency

(creatinine �1.5 mg/dL) 20 (13%) 3 (9%) NSCAS indications

High-risk cardiaccomorbidity 73 (47%) 18 (55%) NS

High-risk pulmonarycomorbidity 12 (8%) 4 (12%) NS

History of neck irradiation 9 (6%) 3 (9%) NSPost-CEA stenosis 17 (11%) 19 (58%) .03High carotid bifurcation 5 (3%) 1 (0.3%) NSStatus post radical neck

dissection 3 (2%) 1 (0.3%) NSCervical fusion 2 (1%) 0 (0%) NSTracheostomy 1 (1%) 0 (0%) NS

CAS, Carotid artery stenting; ISR, in-stent restenosis; NS, not significant;CEA, carotid endarterectomy.

with a 5- or 6-mm balloon catheter. Clinical characteristics

of e

of e

JOURNAL OF VASCULAR SURGERYFebruary 2006308 Zhou et al

of these patients are listed in Table II. Treatment strategiesin these patients are listed in Table III. Four of the sevenpatients had initial stents placed for recurrent stenosis afterCEAs. One patient presented with a transient ischemicattack, and the remaining six patients were asymptomatic.All seven patients underwent endovascular interventions,and the average time interval of reintervention from the

Fig 1. Kaplan-Meier analysis of freedom from 80% orepresent the number of patients at risk at the beginning

Fig 2. Kaplan-Meier analysis of freedom from 60% orepresent the number of patients at risk at the beginning

initial CAS procedure was 14 months (range, 3-20 months).

With regard to endovascular treatment strategies, they in-cluded percutaneous balloon angioplasty alone (n � 1),cutting balloon angioplasty (n � 4), balloon angioplastywith stent placement (n � 1), and cutting balloon angio-plasty (n � 1; Table III). Technical successes, as defined byresolution of the stenosis after treatment, were achieved inall patients, and the mean carotid artery stenosis de-

ater restenosis. Numbers at the bottom of the figureach time period.

ater restenosis. Numbers at the bottom of the figureach time period.

r gre

r gre

creased from 88% to 16% after reintervention. No

JOURNAL OF VASCULAR SURGERYVolume 43, Number 2 Zhou et al 309

procedural-related complications were noted after ISRintervention. During a median follow-up period of 9months after ISR intervention, two patients developedrecurrent stenosis, and additional interventions with acutting balloon angioplasty were successfully performedat 6 and 8 months.

DISCUSSION

The efficacy of CEA has been demonstrated in numer-ous clinical investigations, and CEA continues to be thegold standard for patients with high-grade carotid steno-sis.14,15 However, significant cardiopulmonary morbiditiesand difficult surgical anatomies can potentially increaseprocedure-related complications in a subset of patients whoundergo CEA. Therefore, carotid stenting is advocated asan effective alternative to CEA for this subgroup of pa-tients.3,16 Nonetheless, well-documented hemodynami-cally significant ISR after carotid stenting has raised con-cerns regarding the long-term durability of the procedure.Our study and several others confirmed that the rate ofclinically significant ISR is relatively low.1,8,10-12,17,18 Fur-thermore, our study identified higher incidences of ISR inpatients who had prior CEAs. This highlights that post-CEA stenosis is associated with an increased risk of reste-nosis after stenting and that endovascular intervention forrestenosis is safe and effective.

Several recent prospective clinical trials have docu-

Table II. Clinical characteristics of patients withhigh-grade ISR (�80%)

Variable Data

Total no. patients 7Male sex 6 (86%)Asymptomatic carotid lesion 6 (86%)Symptomatic carotid lesion

Stroke 0 (0%)Transient ischemic attack 1 (14%)Amaurosis fugax 0 (0%)

ComorbiditiesCoronary artery disease 5 (71%)Congestive heart failure 0 (0%)History of myocardial infarction 2 (29%)Smoking 4 (57%)Hypertension 5 (71%)Diabetes 3 (43%)Chronic obstructive pulmonary disease 2 (29%)Hypercholesterolemia 3 (43%)Renal insufficiency (creatinine �1.5 mg/dL) 0 (0%)

CAS indicationsHigh-risk cardiac comorbidity 2 (29%)High-risk pulmonary comorbidity 0 (0%)History of neck irradiation 1 (14%)Post-CEA stenosis 4 (57%)High carotid bifurcation 0 (0%)Status post radical neck dissection 0 (0%)Cervical fusion 0 (0%)Tracheostomy 0 (0%)

ISR, In-stent restenosis; CAS, carotid artery stenting; CEA, carotid endar-terectomy.

mented the efficacy of carotid stenting. As one of the early

clinical investigations on percutaneous carotid interven-tion, the Carotid and Vertebral Artery Transluminal Angio-plasty Study evaluated patients with high-grade carotidstenosis.4 The trial randomized 251 patients with high-grade carotid stenosis to balloon angioplasty and 253 co-hort patients to endarterectomy.4 The incidences of 30-dayand overall disabling stroke or death were similar betweenthe endovascular and surgical groups.4 One significantfinding from this study was markedly reduced operativemorbidity, such as cranial nerve palsy, in the endovasculargroups (0%) compared with the endarterectomy group(8.7%). Similarly, the SAPPHIRE trial confirmed that ca-rotid stenting with distal protection devices was not inferiorto endarterectomy for both asymptomatic patients with80% or greater stenosis and symptomatic patients.5,6 Werecently reported our experiences of carotid stenting withroutine cerebral protection devices in high-risk patients.7

We achieved a 30-day stroke and death rate of 2.7% and anoverall complication rate of 6.9% and did not detect asignificant difference between the symptomatic and asymp-tomatic patients. All stented vessels remained patent duringa mean follow-up of 15 months. These findings werefurther confirmed by this series of 204 patients. Moreover,several multicenter prospective trials are ongoing to evalu-ate the efficacy of CAS. The Carotid RevascularizationEndarterectomy versus Stent Trial randomizes symptom-atic patients who are at low surgical risk to either stenting orendarterectomy.19,20 The trial is expected to enroll 2500patients and to be completed by 2007. The Acculink forRevascularization for Carotids in High Risk Patient Regis-try trial is another ongoing study that is conducted in bothEurope and the United States; it involves 581 consecutivepatients in 3 single arms. The interim results have beenpresented at the annual meetings of the Society of Inter-ventional Radiology and the American College of Cardiol-ogy, but the 1-year data of all three arms are not yetavailable.

Although carotid percutaneous intervention is a safeand effective alternative to CEA, hemodynamically signifi-cant ISR (�80%) after carotid stenting has raised concernsregarding the long-term durability of carotid stenting (Ta-ble IV).8,10-13 Setacci et al12 reported a 3.6% incidence ofhigh-grade restenosis (�80%) during their follow-up ofmore than 372 carotid stents. Similarly, Chakhtoura et al10

reported an 8% high-grade ISR rate during their 18-monthfollow-up of 50 carotid stent procedures. Their slightlyhigher ISR rate is likely reflected by the high percentage ofpatients whose carotid stents were performed for postsur-gical restenosis. The same group later reported a restenosisrate of 5% and predicted a 5-year clinically significant ISRrate of 6.4% by using life-table analysis and Kaplan-Meiersurvival curves.8 Additionally, Willfort-Ehringer et al11 ob-served a 3% high-grade ISR rate during their mean of 12months’ follow-up of 303 Wallstents. Furthermore, theyprospectively evaluated 125 carotid stent procedures byusing ultrasonography and demonstrated that the diame-ters of the self-expanding stents steadily increased over 2

years and that the neointimal thickness increased up to 12

remen

TA, c

JOURNAL OF VASCULAR SURGERYFebruary 2006310 Zhou et al

months and then stabilized thereafter. They thus postu-lated that the complex interaction between neointimalproliferation and stent expansion might contribute to thegood mid-term outcome of carotid stenting.21 Our study,likewise, demonstrated a 3.4% high-grade ISR rate during amean of 17 months’ follow-up among all patients whounderwent carotid stenting. However, the true incidence ofISR in our series is likely to be higher because of a smallpercentage of the patients lost to follow-up, particularlypatients who were referred from outside facilities. Whencomparing medical comorbidities and patient demographiccharacteristics, there were no significant differences be-tween the patients who developed ISR and those withoutsignificant ISR, as demonstrated in Table I. However, ouranalysis of the CAS indications revealed that post-CEAstenosis was associated with an increased risk of poststent-ing ISR (Table I). Similar findings were also recently re-ported by Setacci et al,9 who noted a 3.6% ISR rate after407 CAS procedures. These researchers found that post-CEA restenosis was an independent predictive factor for thedevelopment of ISR. One possible explanation for this

Table III. Treatment strategies and clinical outcome in p

Patientno.

Initial CASindications

PresentingISR symptoms Treat

1 Post-CEA stenosis Asymptomatic PTA (5.5-mm

2 Cardiac morbidity Asymptomatic CB-PTA (6-mm3 Neck irradiation Asymptomatic CB-PTA (5.5-m

and CAS (8-4 Post-CEA stenosis TIA CB-PTA (5-mm

5 Cardiac morbidity Asymptomatic PTA (5-mm baCAS (8-mm

6 Post-CEA stenosis Asymptomatic CB-PTA (5.5-m

7 Post-CEA stenosis Asymptomatic CB-PTA (6-mm

ISR, In-stent restenosis; CAS, carotid artery stenting; CEA, carotid endartepercutaneous transluminal angioplasty; TIA, transient ischemic attack.Degrees of stenosis were calculated by using angiographic calibrated measu

Table IV. Published reports on endovascular intervention

StudyTotal no.patients PTA C

Chakhtoura (2001)10 4 (8%) 3 Willfort-Ehringer (2002)11 9 (3%) 3 Lal (2003)8 4 (4.1%) 3 Chan (2003)27 1Bendok (2003)26 3Tamberella (2004)25 1Setacci (2005)12 15 (3.6%) 3 Levy (2005)13 6 (5%) 5 Current study 7 (3.4%) 1

ISR, In-stent restenosis; PTA, percutaneous transluminal angioplasty; CB-P

phenomenon might be related to the aggressive intimal

hyperplastic reaction in this patient cohort, whether themethod of carotid intervention was endarterectomy orstent placement.

As demonstrated by our study and several other clinicalinvestigations, restenosis after carotid stenting is not un-common, and postprocedural follow-up is essential in iden-tifying patients with hemodynamically significant resteno-sis. Duplex ultrasonography, a standard imaging tool forcarotid artery evaluation, is not as reliable for poststentsurveillance, largely because of a lack of well-establishedultrasound criteria and falsely increased velocities associatedwith increased stiffness of the stented ICA. Ringer et al17

examined their ultrasound criteria for poststent surveillanceand concluded that strict flow velocity criteria for restenosisafter CAS were less reliable than changes in velocity overtime. Similarly, Lal et al22 compared postcarotid stentingultrasound velocity with angiographically measured resid-ual in-stent stenosis and proposed a new criterion thatdefined peak systolic velocity greater than 150 cm/s withICA/CCA greater than 2.16 as the best correlation with agreater than 20% ISR. Our vascular laboratories, likewise,

ts with high-grade ISR

ISR %before

treatment

ISR %after

treatment Outcome

n) 80 20 Restenosis (80%) at 6 motreated with CB-PTA

oon) 90 20 Died of MI at 14 moalloon)iameter)

80 10 No restenosis at 8 mo offollow-up

oon) 98 30 No restenosis at 3 mo offollow-up

) andter)

90 20 No restenosis at 12 mo offollow-up

alloon) 90 5 No restenosis at 8 mo offollow-up

oon) 85 10 Restenosis (80%) at 8 mo,treated with CB-PTA

y; PTA, percutaneous transluminal angioplasty; CB-PTA, cutting balloon

ts.

ISR 80% or greater and follow-ups

ovascular treatment options

Recurrence (mo)TA Stenting Brachytherapy

1 06 2 (3 mo)1 2 (12, 36 mo)

1 01 0

NA8 01 2 (14, 18 mo)2 2 (6, 8 mo)

utting balloon percutaneous transluminal angioplasty; NA, not applicable.

atien

ment

balloo

ballm b

mm dball

lloondiamem b

ball

rectom

s for

End

B-P

214 0 4

have not established standard ultrasound velocity criteria to

JOURNAL OF VASCULAR SURGERYVolume 43, Number 2 Zhou et al 311

evaluate stenosis after carotid stenting because of limitednumber of patients with ISR. Thus, we used a combinationof pre-existing validated velocity criteria in our laboratories(end-diastolic velocity �140 cm/s and CCA/ICA �4correlate with �80% stenosis) and diameter reduction ongrayscale, as well as significant color flow disturbance. Moreimportantly, all hemodynamically significant stenosis basedon sonographic evaluations is further confirmed by carotidangiography before intervention.

Although the optimal treatment of high-grade ISRafter carotid stenting is still controversial, both surgicalintervention and endovascular therapy have been reportedas successful in the literature. Brown et al23 performedbypasses on two patients with high-grade ISR with polytet-rafluoroethylene grafts, whereas de Borst et al24 treatedfour patients by using standard CEA and stent explanta-tion. Nevertheless, surgical intervention is technicallydemanding and potentially associated with substantialprocedural-related complications. Endovascular therapy,conversely, provides the advantage of avoiding previouslystented arteries in high-risk patients. Several endovasculartechniques, including balloon angioplasty, cutting balloonangioplasty, stenting, and, occasionally, brachytherapy,have been described10-13,25-27 (Table IV). Chakhtoura etal10 successfully treated four patients with angioplasty, withor without stenting, and no complication was documentedduring their mean 10 months of follow-up. Similar resultswere reported by Setacci et al12 and Levy et al.13 Con-versely, Willfort-Ehringer21 successfully treated nine pa-tients with endovascular techniques, but two of their pa-tients experienced major cerebral events 17 months later.All our patients were successfully treated with endovasculartechniques, including one patient treated with balloonangioplasty alone, four patients treated with cutting bal-loons, and two patients with additional stent placements.However, two patients required repeat cutting balloonangioplasty 6 and 8 months later for recurrence of hemo-dynamically significant stenosis.

In conclusion, restenosis after CAS is relatively uncom-mon. Our study found that post-CEA stenosis is associatedwith an increased risk of ISR after carotid stenting. Endo-vascular intervention is an effective strategy in the treat-ment of ISR, and repeat intervention may be necessary.Furthermore, our study underscores that routine post-CASsurveillance plays a fundamental role in identifying patientswith hemodynamically significant restenosis, and a prospec-tive randomized trial is warranted to establish reliable post-stenting surveillance criteria.

AUTHOR CONTRIBUTIONS

Conception and design: WZ, PHL, ABLAnalysis and interpretation: WZ, PHL, RBData collection: WZ, MAG, PKWriting the article: WZ, PHLCritical revision of the article: PHL, RLB, EKP, ABLFinal approval of the article: ABLStatistical analysis: WZ, PHL, PK

Overall responsibility: WZ

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3. Veith FJ, Amor M, Ohki T, Beebe HG, Bell PR, Bolia A, et al. Currentstatus of carotid bifurcation angioplasty and stenting based on a con-sensus of opinion leaders. J Vasc Surg 2001;33(2 Suppl):S111-6.

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